The present invention relates to vinyl chloride polymer formulations for medical use. More specifically, the present invention relates to the stabilization of a flexible, plastic vinyl chloride polymer formulation for sterilizable medical devices made from the formulations.
Various polymer formulae can be utilized to create extruded and molded products such as flexible containers, tubing devices and injection molded articles. As examples, flexible containers and tubing devices are utilized in the medical industry for containing and delivering inter alia, parenteral solutions such as intravenous solutions, dialysis solutions, drugs and medications, nutrition products, respiratory therapy products, blood, plasma and other blood related products. When utilized in the medical industry, these products will often contain or contact fluids or solids that are introduced into a patient's body. It is, therefore, necessary for these devices to be essentially transparent; flexible; essentially free of extractables; nonabsorbent of the fluids or solids to be contained; essentially free of particulate matter; and capable of maintaining a product contained therein under sterile conditions until the product is accessed or removed. The plastic material from which these containers, tubing and other articles are constructed must also meet these requirements.
It is also important that the plastic material used in constructing these containers, tubing and other articles is sufficiently strong so that the products constructed from the plastic material have sufficient strength. Furthermore, it is desirable, for economic reasons, that any such plastic material be readily constructed into a container, tubing or other article on commercially available, or easily modified, production machinery. Factors such as production rates, material stabilization, particulate generation, scrap rates and potential regrind are critical considerations in determining the processability of any plastic material used in constructing these types of products.
As set forth above, because the plastic material will be processed into flexible containers and other medical devices that either house or come into contact with a medical product that is introduced into a patient's body, it is necessary that the plastic does not contain chemicals that can be extracted by the medical product or are likely to pass with the medical product into the patient's body. This is especially critical with respect to the various additives to the polymer formulation which are utilized to make the plastic material flexible, generally processable and stable. The toxicity of such additives has been a matter of concern and an area of monitoring.
It has been customary for medical devices such as intravenous solution bags, dialysis containers, blood bags, administration sets and tubing, to be sterilized thermally or by the action of a chemical sterilizing agent such as ethylene oxide gas. In the case of thermal sterilization, however, there has been the problem that the synthetic resin used in such medical containers, tubing and other articles is required to resist thermal degradation. In the case of sterilization with ethylene oxide gas, there has been the problem that, after sterilization, a good deal of time is wasted before the sterilized medical containers, tubing and other articles are free from ethylene oxide gas. As an alternative, sterilization by radiation has been proposed. Since this method is carried out at low temperatures, there is no longer a requirement that the materials of medical containers, tubing and other articles should be capable of withstanding heat and resisting thermal degradation. Nevertheless, radiation may cause such adverse effects as deterioration such as discoloration, haziness when subsequently exposed to water, and increased extractibles of the irradiated medical containers, tubing and other articles unless the plastic materials are properly formulated.
Vinyl chloride polymers ("PVC") have many excellent qualities which make it one of the world's leading commercial plastics. In the medical industry, PVC is widely used in numerous applications including intravenous and drug delivery containers, dialysis containers, blood bags, solution administration sets, tubing and other molded articles. Various plasticizers, stabilizers and other additives have been relied upon in the processing and utilization of PVC for these medical uses but at the acceptance of some other potentially adverse properties. For example, flexible containers and tubing are generally required to have low extractables, low absorption, low water-blush haze, low color, good transparency and should not contaminate fluids carried by the container or tubing with particles. During manufacturing, plasticizers, stabilizers and other additives are utilized during manufacturing for improved processing of PVC, in terms of shorter production times, decreased wear and tear of equipment, absence of particulate matter, low scrap rates and high regrind rates. And ultimately, the PVC container must be stable both during manufacture, processing and use.
PVC's acknowledged weakness is thermal instability during processing and use, resulting in dehydrochlorination and conjugated unsaturation, and leading to increasing discoloration as the length of the conjugation increases. Thermal degradation has been retarded by the addition of a combination of certain selected stabilizers, typically including calcium soap, zinc soap, organo-tin compounds including dialkyl tin esters such as alkyl carboxylic esters (such as laurate and stearate), di(n-octyl)tin maleate polymer and di(n-octyl)tin-S,S'-bis(isooctyl)mercaptoacetate, epoxidized fatty esters and organic phosphite esters.
To meet low amounts of extractable materials required of such medical containers, tubing and other articles, stabilization and processing difficulties may be encountered by degradation of PVC due to low stabilizer content. This low stabilizer content however, has the opposite positive effect by reducing the aqueous extractables from the PVC film. When higher extractables are tolerable or stability of the PVC is more critical, higher amounts of processing aids and stabilizers may be used, but then processing difficulties can be encountered from the plate-out of the excess lubricant or build-up of cross-linked ("cured") epoxides and of other processing aids on the die and chill roll equipment during known extrusion and molding techniques.
Prior attempts at providing a stabilizer system for PVC have been largely unsuccessful due to the incorporation of components that lead to high extractables, poor processability as measured by the plate-out and build-up on equipment, high water-blush haze and high color. For example, U.S. Pat. No. 3,558,539 discloses a stabilizer system for PVC which includes five components including calcium and magnesium salts of a long-chain monocarboxylic fatty acid, a tri-substituted organo monophosphite, and an tri-substituted organo polyphosphite. The addition of these components to a PVC stabilizer system leads to a high water-blush haze upon autoclaving the stabilized PVC film at 121.degree. C., and a high amount of low molecular weight water soluble compounds that lead to a high concentration of extractables.
Another example of a stabilizer system that would lead to high water-blush haze and high extractables is disclosed in U.S. Pat. No. 4,571,118 ("'118"). The '118 Patent discloses a stabilizer system for PVC having a calcium soap, and, among other things, compounds having the formulas OH--X--O--R and R----X--O--R where X is a straight chain, branched or cyclic radical having 2 to about 20 oxygen atoms. These compounds will also lead to high extractables and water-blush haze upon autoclaving the stabilized PVC at 121.degree. C. for one hour.